Effect of choline ester analogues, noradrenaline and nifedipine on normal and hypertrophied human urinary bladder detrusor muscle.
1. Acetylcholine, bethanechol, carbachol and propionylcholine were all agonists of normal human detrusor smooth muscle. The order of potency was found to be carbachol > acetylcholine > bethanachol > propionylcholine. 2. In hypertrophied detrusor smooth muscle carbachol was more potent than acetylcholine, but hypertrophied detrusor preparations were less sensitive to carbachol than normal detrusor smooth muscle. 3. Noradrenaline had no direct effect on either normal or hypertrophied detrusor muscle, but it had a reversible inhibitory effect on the spontaneous contractile activity of normal detrusor preparations. Hypertrophied detrusor preparations usually lacked such spontaneous activity. 4. In calcium-free saline, agonist-induced responses of both normal and hypertrophied detrusor muscle were dramatically reduced indicating that choline ester activity in the muscles was strongly dependent upon extracellular calcium. 5. Nifedipine at 10(-5) mol l-1 inhibited acetylcholine responses and K(+)-induced contractures of both normal and hypertrophied detrusor muscles. Acetylcholine-induced responses of normal detrusor preparations were much more sensitive to inhibition by nifedipine than were the responses of hypertrophied detrusor muscle. 6. The properties and densities of both the muscarinic cholinoreceptors and calcium channels appear to have been altered by the hypertrophic response secondary to benign prostatic hyperplasia.
King
J A
JA
Division of Biological Sciences, Lancaster University, UK.
Huddart
H
H
Staff
W G
WG
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D018723:Bethanechol / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D002794:Choline / Q000031:analogs & derivatives* / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D003470:Culture Media; D004347:Drug Interactions; D006801:Humans; D006984:Hypertrophy / Q000188:drug therapy; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects* / Q000473:pathology*; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology*
D000316:Adrenergic alpha-Agonists; D002121:Calcium Channel Blockers; D018678:Cholinergic Agents; D003470:Culture Media; D018723:Bethanechol; C009062:propionylcholine; D002217:Carbachol; D009543:Nifedipine; D002794:Choline; D000109:Acetylcholine; D002118:Calcium; D009638:Norepinephrine